The overall objectives of this project are to identify distinctive subpopulations of B cells, establish precursor-product relationships between these, and learn something of the kinetics and inductive interactions associated with early differentiative events. Extensive use is made of a simple cloning technique for detecting and characterizing functional murine B cells. Surface Ig negative, pre-B cells become functional in this assay only after a period of preculture in crowded circumstances. On the other hand, a wide variety of sIg-bearing B cells are clonable with the most remarkable exception being cells of immunodeficient CBA/N mice. Clonable cells develop in irradiated or unirradiated CBA/N mice after grafting with chromosomally marked normal cells and manipulations of this system have revealed differences in the capacity of stem cells, fetal pre-B cells, and adult marrow pre-B cells to generate functional B cells. We are attempting to isolate and further characterize these precursor cells and monitor their further maturation in vivo and in vitro with respect to cell surface marker expression and function. Parallel to these studies of normal B-cell development is our continuing analysis of a pre-B like tumor cell line that responds to certain stimuli by synthesizing and exteriorizing surface Ig receptors.